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This article reported two cases of myopathy type very long-chain acyl coenzyme A dehydrogenase deficiency patients, whose clinical manifestations were mainly repeated rhabdomyolysis. In case 1, with fluctuating muscle weakness and myalgia, pathology of skeletal muscle biopsy showed a small amount of degenerative and necrotic muscle fibers, and some muscle fibers had slightly increased fat components. ACADVL gene complex heterozygous mutation was found by second-generation sequencing. Case 2 showed increased polyacylcarnitine and decreased free carnitine by tandem mass spectrometry. Clinical onset muscle weakness, muscle pain and repeat rhabdomyolysis suggested to consider myopathy type very long-chain acyl coenzyme A dehydrogenase deficiency. Because of no specific performance in lower limb muscle magnetic resonance imaging and skeletal muscle biopsy pathology, the case needed to be differentiated from other metabolic myopathy, and tandem mass spectrometry detection and the second generation sequencing are helpful to diagnosis and differential diagnosis.
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Objective To report the clinical and pathological features of one family with neutral lipid storage disease with distal weakness and review the literature , explore the diagnosis and differential diagnosis of the disease , and improve the understanding of the disease .Methods Clinical data of two patients of a family were collected , and next generation sequencing was performed after electrophysiological examination and pathological analysis of skeletal muscle biopsy .And related literature was reviewed .Results Two patients had similar presentations , both having symptoms after 30 years old.The main manifestations were weakness and atrophy of the distal limbs .The creatine kinase levels were increased ( 1067, 740 U/L) .Electromyography revealed myogenic lesions .Pathological analysis of skeletal muscle biopsy showed a large amount of lipid droplets deposition in most muscle fibers .Next generation sequencing revealed a homozygous splice mutation in PNPLA2 gene ( C.187 +1G >A) .Conclusions The two patients with neutral lipid storage disease with myopathy involve distal limbs , which should be distinguished with distal myopathy.The presence of large amounts of lipid droplets in the cytoplasm of muscle fibers can be used for the diagnosis of lipid storage myopathy .The next generation sequencing is helpful for the typing diagnosis of lipid deposition disease .
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Objective Clinical, pathological and molecular biological data of six cases with molecular diagnosis of collagen type Ⅵ related myopathies were retrospectively analyzed to improve the recognition of collagen protein Ⅵrelated myopathy.Methods Clinical and pathological data of six patients diagnosed as collagen protein Ⅵ related myopathy by next generation sequencing and molecular biologic analysis during 2010-2017 were summarized.Results All of the six patients presented early childhood onset ((2.00 ±0.75) years old), and delayed motor growth after birth.There were six cases of proximal muscle weakness , one with distal muscle weakness; three cases with osteoarthropathy; one case of severe skin scar.The creatine kinase levels (187-380 U/L) of three patients were slightly elevated .Three cases showed myogenic damage , two with mild neurogenic lesions , one with myogenic and neurogenic damages . Next generation sequencing showed four cases with COL 6A1 gene heterozygous mutation ( a novel mutation and three had been reported), one with COL6A2 heterozygous mutation and one with COL6A1 and COL6A2 complex heterozygous mutation .The pathological analysis of skeletal muscle biopsy showed that the muscle fiber size was different , and the connective tissue elements were seriously increased .Some opaque fibers were observed.Six cases were found anti-collagen Ⅵ/Ⅳ protein monoclonal antibody immunofluorescence double stained , and sarcolemma Ⅵcollagen protein expression decreased to different degrees .Conclusions The clinical manifestations of the collagen protein Ⅵ related myopathy were found to be complex .Skeletal muscle biopsy pathological analysis was lack of specificity . Anti-collagen Ⅵ/Ⅳ monoclonal antibody immunofluorescence double staining showed collagen protein Ⅵ missing partly or completely . Immunofluorescence staining and the next generation sequencing can improve the diagnosis of collagen proteinⅥrelated myopathy.
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Objective To estimate the consistency between the diagnostic criteria for dermatomyositis (DM) and polymyositis (PM) developed by Bohan and Peter criteria (B/P criteria) and ENMC criteria.Methods The clinical,laboratory and pathological data from 86 patients who were initially diagnosed with idiopathic inflammatory myopathy were collected retrospectively.These patients were diagnosed according to B/P criteria and ENMC criteria,and the similarities and differences between these two criteria were compared.The data were analyzed with Mann Whitney U test and Kappa test by SPSS 13.0 software.Results Thirtyseven DM and 49 PM were diagnosed using B/P criteria.Forty-six DM and 14 PM were diagnosed using ENMC criteria,and 1 was diagnosed as eosinophilic myositis,9 were diagnosed as sporadic inclusion body myositis (sIBM),11 cases were diagnosed as limb-girdle muscular dystrophy type 2B,and the diagnosis of 5 patients could not be clarified.Agreement for DM between these two sets of criteria was very good by Kappa test (κ=0.79),but the corresponding between the two tests for PM was poor (κ=0.26).Conclusion Our study has demonstrated that B/P criteria may cause over-diagnosis and misdiagnosing for PM.ENMC criteria involves immunohistochemical pathology,stratified clinical and pathological exclusion criteria.The diagnostic accuracy of ENMC criteria is much improved.
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Objective To analyze retrospectively the clinical manifestations,features of the biopsy of skeletal muscle with histochemistry and immunohistochemistry staining of 40 patients with dysferlinopathy and investigate its clinical,pathological diagnostic value.Methods The clinical data,features of the biopsy of skeletal muscle with histochemistry,immunohistochemistry staining of 40 patients with dysferlinopathy were analyzed.Results Chronic progressive weakness and wasting were the general clinical manifestations.In our study,it was divided into three phenotypes according to the involved muscles of dysferlinopathy:27 cases with proximal muscle,12 cases with the gastrocenemius,1 case with the tibialis anterior muscle.The serum creatine kinase levels all had a rise in different degree (134-19 795 U/L).All the patients showed myogenic lesions in electrophysiologic study.12 patients underwent skeletal muscle MRI.Proximal muscle was involved in 4 cases ; gastrocnemius muscle was mainly involved in 7 cases ; and anterior tibial muscle initially was involved in 1 case.All 40 cases showed active muscle fiber degeneration,necrosis and regeneration on muscle pathology.Connective tissues were proliferated and inflammatory cells infiltrated in endomysium,perimysium and perivascular sites of 16 patients.Immunohistochemical staining with anti-dysferlin monoclonal antibody identified the deficiency of dvsferlin in the sarcolemma of 30 cases with dysferlinopathy,and dysferlin was severely reduced in 10 cases.Conclusion Progressive weakness and wasting of skeletal muscle are the clinical manifestations of dysferlinopathy.The early involved muscles determine the clinical phenotype of dysferlinopathy.High serum creatine kinase levels show that dysferlinopathy is a membrane protein null disease.Muscle MRI of lower limbs may reflect the involved muscles,which is essential for clinical phenotypes and selecting muscle biopsy.The pathological characters of dysferlinopathy are changes of muscular dystrophy.Inflammatory cellular infiltration is relatively common in biopsied muscles of many dysferlinopathy patients,and dysferlinopathy needs to be differentiated from inflammatory myopathies.The deficiency or severely decreased dysferlin on the sarcolemma in immunohistochemical staining with anti-dysferlin monoclonal antibody is an important information for diagnosing dysferlinoapthy.
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Objective To analyze the clinical and laboratory phenotypes of Duchenne muscular dystrophy(DMD)in a retrospective study of 96 cases and to evaluate therapeutic efficacy of glucocorticosteroid.Methods The clinical phenotype,laboratory examinations resuhs and the records in the follow-up in 96 patients with DMD were collected.The level of serum creatine kinase(CK)and motor ability before and after glucocorticosteroid therapy were analyzed by statistical analysis.Their myocardium impairments and intelligence conditions were also assessed.Results(1)The level of serum CK (mmol/L)had three peaks at the age of ≤ 3 years old(16 547.9 ±770.9),5 years old(14 371.9 ± 696.7)and 8 years old(13 089.8 ± 877.6).The CK level significantly decreased after dexamethasone (5-10 mg,iv)treatment for 10-15 days,but increased again after prednisone acetate(0.50-0.75 mg · kg-1 · d-1,oral)administration for one month(F =6.758,P =0.003).(2)The motor ability improved in 51 DMD cases with long-term oral admission of prednisone,including 24 cases receiving repeated dexamethasone,iv.(3)The myocardial perfusion imaging in 37 DMD cases showed remarkable uneven “spotted like” radionuclide distribution in ventricle.(4)The intelligence quotients in 24 DMD were lower than normal population.Conclusions There are high CK hyperlipidemia and myocardial damage in the sub-clinical stage of DMD and myocardium impairment is positively correlated with age.Glucocorticosteroid therapy has an important effect on the protection of motor and cardiac functions,with recommendation of using in early stage of disease.
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Objective To study the clinical and pathological features of periodic paralysis.Methods The clinical and pathological data of 9 patients with periodic paralysis were analyzed.Results The clinical manifestation of 9 patients were consistent with the general manifestation of periodic paralysis.The typical tubular aggregates in many fibers were observed in 4 cases of 7 patients with skeletal muscle biopsy.A few degenerating fibers were observed,while necrotic fibers and regenerating fibers were not found.Electromicroscope showed Honeycomb appearance in tubular aggregates of cross section,which was filled with glycogen granule.Conclusions According to the clinical manifestation and the laboratory examination,periodic paralysis can be clinical diagnosis.The tubular aggregates in many fibers are important pathological characteristic of periodic paralysis.In electromicroscope analysis,tubular aggregates may be compose of transverse tubular system or sarcoplasmic reticulum expansion.